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Volume 6 Issue 7, July 2014

Proteins can adopt many conformations at room temperature, which creates a problem for those trying to find complementary ligands. Now, James S. Fraser, Brian K. Shoichet and colleagues have developed a computational method that represents the conformational behaviour of proteins in docking screens. An artistic impression of the docking of nine newly discovered ligands within a protein binding site is shown on the cover; the panels are arranged in pairs and depict either a prediction of a particular ligand-protein interaction (upper) or the corresponding crystallographic data (lower).Article p575;News &#38; Views p560IMAGE: RYAN G. COLEMAN

Thesis

Michelle Francl suggests that students should be trained to write in a fashion similar to how they are taught the principles and practice of NMR spectroscopy — by providing them with a limited set of patterns and parameters.

Blogroll

News and Views

The flexibility and structural dynamics of proteins pose a big challenge for those trying to discover new bioactive compounds. Now, by using guiding crystallographic data, a method that uses the energetic balance between protein conformers to weight docking scores is shown to aid the hunt for new ligands.

The palladium-catalysed cross-coupling of aryl- or alkenylboronates and aryl halides has proved phenomenally successful for the formation of Csp2–Csp2 bonds. Now, an alternative non-transition-metal-mediated coupling using similar reactants has been reported for the stereo-controlled formation of Csp2–Csp3 bonds.

Protein-based protonic conductivity plays an important role in nature, but has been explored little outside of a biological setting. Now, proton conductors have been developed based on the squid protein reflectin, and integrated with devices for potential bioelectronic applications.

The ordered one-dimensional nanochannels found in covalent organic frameworks (COFs) could render them able to conduct protons. However, the frameworks' instability in acid has thus far precluded any practical implementations. Now, a strategy to overcome this instability has enabled proton conduction using a COF for the first time.

Live-attenuated viruses used in vaccines can regain their virulence, which for deadly viruses such as HIV is an unacceptable risk. Now, attenuated HIV-1 viruses, which include mutations that genetically encode unnatural amino acids and prevent them from replicating in normal cells, have been constructed.

Shixian Lin

& Peng R. Chen

Perspective

RNA can carry information, self-replicate and catalyse reactions, and so is often included in scenarios for the origin of life, but was it the first self-replicator? This Perspective considers the question of whether simpler polymer structures could have encoded early life, and discusses how to seek them out.

Ashley Brewer

& Anthony P. Davis

Articles

The adoption of multiple conformations by proteins presents a challenge for ligand discovery using docking simulations. Now, a method for representing the conformational behaviour of a flexible protein in docking screens, which is guided by experimental crystallography data, is shown to predict protein conformation, ligand pose and aid the discovery of new ligands.

A general and broad-ranging stereospecific coupling of secondary and tertiary boronic esters with electron-rich aromatics is reported. The reaction involves initial formation of a boronate complex followed by activation of the electron-rich aromatic moiety by an electrophile, which triggers a stereospecific 1,2-migration and subsequent elimination/re-aromatization.

Selective functionalization of light hydrocarbons is a challenging but desirable transformation. Now a family of Fe(II)-based metal–organic frameworks has been shown to convert ethane into ethanol and acetaldehyde using N2O. Electronic structure calculations indicate that the active Fe oxidant in the MOF is a high-spin S = 2 iron(II)–oxo species.

Proton-conducting materials have proved useful for renewable energy applications and bioelectronics technologies. The proton conductivity of thin films made from reflectin — a cephalopod structural protein — is now reported. Reflectin's electrical properties compare favourably to those of artificial materials, and have enabled the demonstration of protein-based protonic transistors.

A nanoreactor approach has now been used to investigate the substitution reactions of arsenic(III) compounds with thiols at the single-molecule level. The rates of interconversion of seven reaction components are tracked, revealing the stereochemistry of sulfur–sulfur substitution at an arsenic centre.

Most cyclic conjugated molecules, such as benzene, exhibit two sides. Möbius annulenes, however, with an odd number of 180° twists in their π system, are one-sided and violate the Hückel rule. Now, using a topological trick it is demonstrated that triply twisted systems are not particularly strained and probably easier to synthesize than singly twisted ones.

Tyrosine-kinase inhibitors (TKI) are amongst the best known examples of targeted cancer therapeutics. Now, using hyperspectral stimulated Raman scattering imaging, the label-free visualization and quantification of two TKI drugs inside living cells is reported. Significant trapping of TKI drugs in lysosomes was observed, which can be reversed by co-treatment with chloroquine through lysosome-mediated interactions.

Strong acoustic fields applied to solutions of linear polymers typically result in mid-chain scission, yielding products half the molecular weight of the original. Now it has been shown that poly(o-phthalaldehyde), a polymer with a ceiling temperature below room temperature, undergoes chain scission and subsequent depolymerization to monomers. Introduction of an appropriate initiator to the monomer regenerates poly(o-phthaladehyde) macromolecules.

Magnetic resonance imaging of gene expression has been limited by the low molecular sensitivity of conventional 1H-MRI. To overcome this limitation, the first genetically encoded reporters for hyperpolarized xenon MRI have been developed. These expressible reporters, based on gas-filled protein nanostructures from buoyant microorganisms, are detectable at picomolar concentrations.

Adjuvants are used to increase the immune response to molecular vaccines. A minimal synthetic variant of the saponin natural product QS-21 has been developed as a potent, non-toxic adjuvant, enabling dissection of structural requirements in the triterpene domain and in vivo biodistribution studies to probe mechanisms of action.

Studies of the Earth's atmosphere have shown that more than 90% of xenon is depleted — the so-called missing Xe paradox. Now a theoretical study shows that Xe and Fe/Ni can form inter-metallic compounds of XeFe3 and XeNi3 under conditions found in the Earth's inner core, and could provide a solution to the puzzle.

In Your Element

Alfred Nobel's eponymous element, nobelium, was 'first' discovered either in the 1950s or 1960s, in the USSR, Sweden or the USA. Brett F. Thornton and Shawn C. Burdette delve into the ensuing decades of internecine strife over the discovery of element 102.